#MSCOVID19 what use is this research to my MS? Anti-drug antibody testing


Below is work from DrRuth at BartsMS and our friends in Wales and elsewhere. This study shows that people taking fingolimod and anti-CD20 depleting antibodies dont’ make a good COVID-19 vaccine responses. You know this already as we reported this some time ago when the paper was first submitted to MedRXiv. This result has been replicated over and over again, but the work is a collaboration between our neuros and I will give a shout out to Cambridge too how where doing their own thing but kept everyone in the loop. The approach by Cardiff and Barts health was not to get people into hospital to give blood but to use blood spot cards to sample people remotely.

When COVID-19 lock-down occurred we were kicked out of the labs and could only work on COVID-19, so rather that twiddle our thumbs we applied the new technology from ProfAngry to do this. We had previously worked with Dr Tallantyre and the Cardiff group to look at anti-drug antibodies to alemtuzumab.

Saxena G, Moore JM, Jones M, Pryce G, Ali L, Leisegang GR, Vijay V, Loveless S, Robertson NP, Schmierer K, Giovannoni G, Gnananpavan S, Baker D, Tallantyre EC, Kang AS. Detecting and predicting neutralization of alemtuzumab responses in MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e767.

We finished the first element of work when the pandemic hit.

We have been detecting covid-19 response following infection and after vaccination, but what is the advantage for MS. Well originally we were working of blood samples and we showed it could work for blood spots.

So moving forward we can measure anti-drug antibodies respondes in blood spots.

So the next bit of the advnture is to make the tools to detect anti-drug responses for other MS agents and am please to say that our collaborations will continue for the next bit of the story

Tallantyre EC, Vickaryous N, Anderson V, Asardag AN, Baker D, Bestwick J, Bramhall K, Chance R, Evangelou N, George K, Giovannoni G, Godkin A, Grant L, Harding KE, Hibbert A, Ingram G, Jones M, Kang AS, Loveless S, Moat SJ, Robertson NP, Schmierer K, Scurr MJ, Shah SN, Simmons J, Upcott M, Willis M, Jolles S, Dobson R. COVID-19 vaccine response in people with multiple sclerosis. Ann Neurol. 2021 Oct 22. doi: 10.1002/ana.26251. Epub ahead of print. PMID: 34687063.

Objective: To investigate the effect of disease modifying therapies on immune response to SARS-CoV2 vaccines in people with multiple sclerosis.

Methods: 473 people with multiple sclerosis provided one or more dried blood spot samples. Information about COVID-19 and vaccine history, medical and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2. Antibody titres were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response.

Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.04; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly associated with response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Preliminary data on cellular T-cell immunity showed 40% of seronegative subjects had measurable anti-SARS-CoV2 T cell responses.

Interpretation: Some disease modifying therapies convey risk of attenuated serological response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. 

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.

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  • Which seronegative subjects had measurable anti-SARS-CoV2 T cell responses? Any data on how those who did and those who didn’t people break down? Vaccine brands, etc?

    • For most MS DMT there is no issue the people who are seronegative are on anti-CD20 and they have a T cell response, those on fingolimod have neither detectable:-(

      The Astrazeneca in my mind is one issue and I am afraid there were more seronegative people with AZA so get booster of something else…This not just MS, I suspect that many double vaxed people will get infected.

  • Developing ADA blood spot tests that are stable enough to be put in the mail/post is an amazing achievement and a huge step forward in patient care. Well done! Not to mention the ALEM de-risking research that was published with the help of the data obtained from ADA tests.

    Pre-pandemic when I was having issues with OCR, I could not find a doctor in the U.S. that would take the time (or effort) to mail some of my actual blood across the pond. Happy to hear the technology has advanced and will become more accessible to patients in the future.

    The “all mighty MS Society” (sarcasm added) should fund a program where every pwms is given access to a blood spot test.

    Somewhat sad a global pandemic had to be the catalyst to push this innovation and collaborative effort forward. However, I guess sometimes a bad situation does yield unexpected results.

    Thank you for the update MD1.

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